tetano
Editor, Senior Moderator
Am J Respir Crit Care Med. 2016 Mar 9. [Epub ahead of print]
[h=1]Syndecan-1 Attenuates Lung Injury During Influenza Infection By Potentiating c-Met Signaling to Suppress Epithelial Apoptosis.[/h] Brauer R[SUP]1[/SUP], Ge L[SUP]2[/SUP], Schlesinger SY[SUP]3[/SUP], Birkland TP[SUP]4[/SUP], Huang Y[SUP]5[/SUP], Parimon T[SUP]6[/SUP], Lee V[SUP]7[/SUP], McKinney BL[SUP]8[/SUP], McGuire JK[SUP]9[/SUP], Parks WC[SUP]10[/SUP], Chen P[SUP]11[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] [h=4]RATIONALE:[/h] Syndecan-1 is a cell surface heparan sulfate proteoglycan primarily expressed in the lung epithelium. Because the influenza virus is tropic to the airway epithelium, we investigated the role of syndecan-1 in influenza infection.
[h=4]OBJECTIVE:[/h] To determine the mechanism by which syndecan-1 regulates the lung mucosal response to influenza infection.
[h=4]METHODS:[/h] WT and Sdc1-/- mice were infected with a H1N1 virus (PR8) as an experimental model of influenza infection. Human and murine airway epithelial cell cultures were also infected with PR8 to study the mechanism by which syndecan-1 regulates the inflammatory response.
[h=4]MEASUREMENT AND MAIN RESULTS:[/h] We found worsened outcomes and lung injury in Sdc1-/- mice compared to WT mice after influenza infection. Our data demonstrate that syndecan-1 suppresses bronchial epithelial apoptosis during influenza infection to limit widespread lung inflammation. Furthermore, we determined that syndecan-1 attenuated apoptosis by crosstalking with c-Met to potentiate its cytoprotective signals in airway epithelial cells during influenza infection.
[h=4]CONCLUSIONS:[/h] Our work shows that cell-associated syndecan-1 has an important role in regulating lung injury. Together, our findings demonstrate a novel mechanism in which cell membrane-associated syndecan-1 regulates the innate immune response to influenza infection by facilitating cytoprotective signals through c-Met signaling to limit bronchial epithelial apoptosis thereby attenuating lung injury and inflammation.
[h=4]KEYWORDS:[/h] Influenza, lung injury, syndecan-1, proteoglycan, c-Met
PMID: 26959387 [PubMed - as supplied by publisher]
[h=1]Syndecan-1 Attenuates Lung Injury During Influenza Infection By Potentiating c-Met Signaling to Suppress Epithelial Apoptosis.[/h] Brauer R[SUP]1[/SUP], Ge L[SUP]2[/SUP], Schlesinger SY[SUP]3[/SUP], Birkland TP[SUP]4[/SUP], Huang Y[SUP]5[/SUP], Parimon T[SUP]6[/SUP], Lee V[SUP]7[/SUP], McKinney BL[SUP]8[/SUP], McGuire JK[SUP]9[/SUP], Parks WC[SUP]10[/SUP], Chen P[SUP]11[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] [h=4]RATIONALE:[/h] Syndecan-1 is a cell surface heparan sulfate proteoglycan primarily expressed in the lung epithelium. Because the influenza virus is tropic to the airway epithelium, we investigated the role of syndecan-1 in influenza infection.
[h=4]OBJECTIVE:[/h] To determine the mechanism by which syndecan-1 regulates the lung mucosal response to influenza infection.
[h=4]METHODS:[/h] WT and Sdc1-/- mice were infected with a H1N1 virus (PR8) as an experimental model of influenza infection. Human and murine airway epithelial cell cultures were also infected with PR8 to study the mechanism by which syndecan-1 regulates the inflammatory response.
[h=4]MEASUREMENT AND MAIN RESULTS:[/h] We found worsened outcomes and lung injury in Sdc1-/- mice compared to WT mice after influenza infection. Our data demonstrate that syndecan-1 suppresses bronchial epithelial apoptosis during influenza infection to limit widespread lung inflammation. Furthermore, we determined that syndecan-1 attenuated apoptosis by crosstalking with c-Met to potentiate its cytoprotective signals in airway epithelial cells during influenza infection.
[h=4]CONCLUSIONS:[/h] Our work shows that cell-associated syndecan-1 has an important role in regulating lung injury. Together, our findings demonstrate a novel mechanism in which cell membrane-associated syndecan-1 regulates the innate immune response to influenza infection by facilitating cytoprotective signals through c-Met signaling to limit bronchial epithelial apoptosis thereby attenuating lung injury and inflammation.
[h=4]KEYWORDS:[/h] Influenza, lung injury, syndecan-1, proteoglycan, c-Met
PMID: 26959387 [PubMed - as supplied by publisher]